Cortactin regulates cell migration through activation of N-WASP

被引:105
作者
Kowalski, JR
Egile, C
Gil, S
Snapper, SB
Li, R
Thomas, SM [1 ]
机构
[1] Harvard Univ, Sch Med, Canc Biol Program, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA
[3] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02215 USA
[4] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA
[5] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02215 USA
关键词
cortactin; N-WASP; SH3; domain; cell migration; actin polymerization;
D O I
10.1242/jcs.01586
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cortactin is an actin-associated scaffolding protein that regulates cell migration. Amplification of the human gene, EMS1, has been detected in breast, head and neck tumors, where it correlates with increased invasiveness. Cortactin can regulate actin dynamics directly via its N-terminal half, which can bind and activate the Arp2/3 complex. The C-terminal portion of cortactin, however, is thought to have limited function in its regulation of the actin polymerization machinery. In this report, we identify a role for the cortactin C-terminus in regulating cell migration and, more specifically, actin dynamics. Overexpression of either full-length cortactin or cortactin C-terminus is sufficient to enhance migration of mammary epithelial cells. In vitro, cortactin binds to and activates, via its SH3 domain, a regulator of the Arp2/3 complex, neural Wiskott Aldrich Syndrome protein (N-WASP). This in vitro activation of N-WASP is likely to be important in vivo, as cortactin-enhanced migration is dependent upon N-WASP Thus, our results suggest that cortactin has multiple mechanisms by which it can recruit and modulate the actin machinery and ultimately regulate cell migration.
引用
收藏
页码:79 / 87
页数:9
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